1 Boring Old Man

Controversial Paxil paper still under fire 13 years later

Some say former U. professor Martin Keller’s paper was ghostwritten and should be retracted

The Brown Daily Herald

By Isobel Heck

April 2, 2014

Former University Professor Martin Keller published a 2001 paper on the drug Paxil that has allegedly been ghostwritten by GlaxoSmithKline.

Two weeks ago, Edmund Levin and George Stewart, members of the American Academy of Child and Adolescent Psychiatry, sent a letter to the editor of the Academy’s journal, requesting an explanation as to why a controversial study led by former Brown Professor Emeritus of Psychiatry and Human Behavior Martin Keller has not been retracted.

The paper — which details the findings of Study 329 and focuses on the effects of the drug Paxil on adolescent depression — has been continually criticized since its publication in 2001.

While Levin and Stewart have worked to get the paper retracted, Jon Jureidini, a professor at the University of Adelaide in Australia and a member of the nonprofit Healthy Skepticism, has been working with his team to reanalyze the original data and republish the results…

There are a number of reasons study 329 percolated to the top of the pile as an example of the widespread scientific misbehavior in clinical trial reporting. It was about using medication in children. It is an obviously jury-rigged report on first reading. It was authored by an army of top level child psychiatrists and published in a first line journal. One wonders why the authors, the company [GSK], and the Journal [Journal of the American Academy of Child and Adolescent Psychiatry] hasn’t  simply retracted it and  moved on. Instead, they persist in their denial.

Medical school leaders cash in on drug company boards

Milwaukee Journal Sentinel

By John Fauber

April 1, 2014

While university doctors who moonlight for drug companies have faced intense scrutiny in recent years, new research suggests much larger sums of money are being paid to their bosses — the leaders of medical schools and hospitals who serve on drug company boards. Looking at the world’s 50 largest drug companies, researchers found that 40% had at least one board member who held a leadership position at a U.S. academic medical center — including medical school deans, chief executive officers, department chairs and university presidents.

The average annual compensation from the drug companies was $313,000, according to the paper published today in the Journal of the American Medical Association. "These relationships present potentially far-reaching consequences beyond those created when individual physicians consult with industry or receive gifts," the researchers wrote.

Others who were not a part of the paper said such lucrative moonlighting for drug companies with vested interests simply should not be done by university leaders who oversee independent research and the instruction of medical practitioners…

hat tip to Pharmagossip…

^{from JAMA 2014 311[13]:1353-1355.}

DSM-5 Field Trials in the United States and Canada, Part II: Test-Retest Reliability of Selected Categorical Diagnoses and Analytic Approaches

by Darrel A. Regier, William E. Narrow, Diana E. Clarke, Helena C. Kraemer, S. Janet Kuramoto, Emily A. Kuhl, and David J. Kupfer

American Journal of Psychiatry. 2013 170:59-70.

[full text on-line]

… Emil Kraepelin, who pioneered the separation of schizophrenic and affective psychoses into separate diagnostic groups in 1898, noted later in a 1920 publication — prescient in its anticipation of a current polygenetic environmental interaction model of mental disorders — that the strict separation of these categorical diagnoses was not supported. We are now coming to the end of the neoKraepelinian era initiated in the U.S. by Robins and Guze with a renewed appreciation of both the benefits and limitations of a strict categorical approach to mental disorder diagnosis.

The ultimate goal is to build on the progress achieved with categorical diagnoses by continuing with longitudinal follow-up of patients with these diagnoses, incorporating cross-cutting dimensional measures judiciously into the diagnoses where they prove useful, and in some cases recommending simple external tests [such as a cognitive test for mild neurocognitive disorder] that might improve the reliability and move toward a more mature scientific understanding of mental disorders. A noted philosopher of science, Carl Hempel, observed that “although most sciences start with a categorical classification of their subject matter, they often replace this with dimensions as more accurate measurements become possible”.

Clinicians think dimensionally and adjust treatments to target different symptom expressions in patients who may have the same categorical diagnosis. The intent of DSM-5 is to provide a diagnostic structure that will more fully support such dimensional assessments with diagnostic criteria revisions, specifiers, and cross-cutting symptom domain assessments. The goal is to support better measurement-based care and treatment outcome assessment in an era when quality measurement and personalized medicine will require new diagnostic approaches."

At the time this was written, the Task Force had given up on the attempt to add in biological parameters to the DSM-5 [Neuroscience, Clinical Evidence, and the Future of Psychiatric Classification in DSM-5], but their hopes for the cross-cutting dimensions were still alive. I had taken  cross-cutting dimensions to mean symptoms that crossed diagnostic entities, but I think there was more to it. They were actually looking for anything that could be measured or quantified, like the kind of thing Madhukar Trivedi was so obsessed with – called measurement based care. Reading it now, it seems as if the practice they were planning for psychiatrists was modeled on the Clinical Trial motif [rather than the other way around], and the measurement would be like those in Clinical Trials –  a psychometric of some kind – as in the example above. In fact, we know that’s what they meant from Jane Costello’s DSM-5 resignation letter [summer of 09]:

When I look at my timeline of the Affair d’Kupfer, it seems impossible not to conclude that their company with its Computerized Adaptive Testing had been planned to take advantage of the addition of dimensional measures to the DSM-5 from the very start. Insider trading, profiteering, whatever you want to call it, it’s a huge conflict of interest. So one part of my reading of this article was that it strengthened my suspicions of unethical play by Dr. Kupfer and his colleagues.

And while I’ve never been in love with the DSM-anything, it seems to me as if something kind of sleazy went on here that needs to see the light of day. This agenda for the DSM-5 was set over a decade ago. It was at a time when Steven Hyman was Director of the NIMH. And, as a matter of fact, Darrell Regier, who later became Co-Chair of the DSM-5 Task Force was coming to the end of a 25 year career at the NIMH. So somewhere around 2002, Steven Hyman agreed for the NIMH to go in with the APA to fund a long series of symposia based of their agenda for the DSM-V/5; Darrell Regier went from the NIMH to APIRE [American Psychiatric Institute for Research and Education] part of the American Psychiatric Foundation where he has primarily worked on the DSM-5; they published the A Research Agenda for the DSM-5; and, oh yeah, Dr. Robert Gibbons began to work on his CAT psychometrics funded by the NIMH. It now appears to me that there was a grand plan here – a grand plan to use the DSM-5 Revision to effect a major paradigm shift in psychiatry just like the DSM-III had been used in 1980 – a grand plan hatched by the power players at the NIMH, the APA, and the APF. History was going to repeat itself.

So no wonder they tried to wave off Drs. Spitzer and Frances. Those guys were still thinking about categories and reliability. They didn’t want their input. They wanted them to get out of the way of the new version of the new psychiatry. No wonder they spent so little time looking at the categories that were in need of work. They weren’t interested in descriptive categories anymore. Little surprise that they appointed an Instrument Assessment Study Group to come up with ways to measure dimensions. That was the plan in the first place. And perhaps it also explains the most striking feature of this DSM-5 Task Force. They were impervious to infuence from anything – huge changes in the climate of psychiatry, scandals galore, a major rebellion in the public forum, the exit of  PHARMA from the scene, failed Field Trials. Nothing had any impact on their course. They were on a predefined mission.

In the last post, referring to the Schatzberg, Scully, Kupfer, Regier letter in respsonse to Dr. Frances, I said, "That’s the low point of this story for me – a school playground bully response that has no place in any serious dialog." But in another way, it was a high point for the DSM-5 Revision enterprise, because after that, everything just seemed to continue to roll down hill.

For one thing, at around this same time, Senator Grassley’s investigation of prominent psychiatrists who had under-reported their outside income was moving ahead full steam. And with that came the more widespread exposure of the research and marketing misconduct involving academic psychiatrists and the Pharmaceutical industry – along with legal suits that flushed out a stream of incriminating documents from the discovery process. If there had ever been a time for organized psychiatry to eat some humble pie, this was it. But that was not to be. In fact, the President of the APA was, himself, on Senator Grassley’s bad-boy list and one of the authors of the nastygram in response to Dr. Frances – Dr. Alan Schatzberg of Stanford.

I don’t need to say anything about Dr. Frances’ campaign and the overwhelming support it received from outside psychiatry. You read about it in the popular media: Psychology Today, Psychiatric Times, Huffington Post. There is a point I would make about it. Frances’ original complaint was primarily about the process of the DSM-5 Task Force, but the general reaction was more to some of the suggested diagnostic changes, to the exclusively biological focus, and to the suggested motive of the promotion of medications. While I wouldn’t argue with any of those things, there wasn’t much discussion of the actual Revision of the Diagnostic and Statistical Manual of Mental Illnesses. There were many places where the system had glaring problems that were even bigger than the limitations inherent in a descriptive classification. Two that come to mind are Major Depressive Disorder and Generalized Anxiety Disorder that were being used loosely in practice as synonyms for unhappy person and nervous person. My point? The main purpose of the revision got lost is the process.

Neuroscience, Clinical Evidence, and the Future of Psychiatric Classification in DSM-5

by David J. Kupfer, M.D. and Darrel A. Regier, M.D., M.P.H.

American Journal of Psychiatry 168:672-674, 2011.

[full text online]

DSM-5: How Reliable Is Reliable Enough?

by Helena Chmura Kraemer, David J. Kupfer, Diana E. Clarke, William E. Narrow, and Darrel A. Regier

American Journal of Psychiatry 2012 169:13-15.

[full text online]

A Comparison of DSM-IV and DSM-5 Panel Members’ Financial Associations with Industry:

A Pernicious Problem Persists

PLoS Medicine

by Lisa Cosgrove and Sheldon Krimsky

March 13, 2012

[full text online]

By the time the Board of Trustees was given the final draft,  many of the really shaky additions had fallen by the wayside [like the Attenuated Psychosis Syndrome] and they’d given up on the dream of adding the biomarkers and biological correlates to the mix [because there weren’t any]. The fact that the parts of the DSM-IV that had needed an overhaul had been ignored was itself ignored. The only thing left of the grand plan from the 2002 book [A Research Agenda for the DSM-V] or the 2009 Commentary [The Conceptual Development of DSM-V] was the addition of "Dimensions" to the diagnostic scheme. The Board of Trustees wisely said no to the proposed version.

"They plotted a revolution, fell to debating among themselves, and in the end overturned very little except their own expectations…" "… many experts inside and outside the process said the final document was not radically different from the previous version, and its lessons more mundane than the rhetoric implied."

But, Mousie, thou art no thy lane,
In proving foresight may be vain;
The best-laid schemes o’ mice an’ men
Gang aft agley,
And lea’e us nought but grief an’ pain
For promised joy!

To a Mouse On Turning her up in her Nest with the Plow by Robert Burns

The Conceptual Development of DSM-V

by Darrel A. Regier, William E. Narrow, Emily A. Kuhl, and David J. Kupfer

American Journal of Psychiatry. 2009 166:645-650.

[full text online]

The single most important precondition for moving forward to improve the clinical and scientific utility of DSM-V will be the incorporation of simple dimensional measures for assessing syndromes within broad diagnostic categories and supraordinate dimensions that cross current diagnostic boundaries. Thus, we have decided that one, if not the major, difference between DSM-IV and DSM-V will be the more prominent use of dimensional measures in DSM-V.

… we have come to understand that we are unlikely to find single gene underpinnings for most mental disorders, which are more likely to have polygenetic vulnerabilities interacting with epigenetic factors [that switch genes on and off] and environmental exposures to produce disorders.

A Warning Sign on the Road to DSM-V: Beware of Its Unintended Consequences

Psychiatric Times

by Allen Frances

June 26, 2009

[full text online]

My concerns arise from the following:

• Their ambition to achieve a paradigm shift when there is no scientific basis for one.
• Their failure to provide clear methodological guidelines on the level of empirical support required for changes.
• Their lack of openness to wide scrutiny and useful criticism.
• Their inability to spot the obvious dangers in most of their current proposals.
• Their failure to set and meet clear timelines.
• The likelihood that time pressure will soon lead to an unconsidered rush of last-minute decisions.

This is the first time I have felt the need to make any comments on DSM-V. Even when the early steps in the DSM-V process seemed excessively ambitious, secretive, and disorganized, I hoped that I could avoid involvement and believed that my successors deserved a clear field. My unduly optimistic assumption was that the initial problems of secrecy and lack of explicitness would self-correct and that excessive ambitions would be moderated by experience. I have decided to write this commentary now only because time is running out and I fear that DSM-V is continuing to veer badly off course and with no prospect of spontaneous internal correction. It is my responsibility to make my worries known before it is too late to act on them…

Setting the Record Straight: A Response to Frances Commentary on DSM-V

Psychiatric Times

By Alan F. Schatzberg, James H. Scully Jr, David J. Kupfer, and Darrel A. Regier.

July 01, 2009

[full text online]

Finally, Dr. Frances opened his commentary with the statement, “We should begin with full disclosure.”  It is unfortunate that Dr. Frances failed to take this statement to heart when he did not disclose his continued financial interests in several publications based on DSM-IV.  Only with this information could the reader make a full assessment of his critiques of a new and different DSM-V.  Both Dr. Frances and Dr. Spitzer have more than a personal “pride of authorship” interest in preserving the DSM-IV and its related case book and study products. Both continue to receive royalties on DSM-IV associated products. The fact that Dr. Frances was informed at the APA Annual Meeting last month that subsequent editions of his DSM-IV associated products would cease when the new edition is finalized, should be considered when evaluating his critique and its timing.

As documented in the recent American Journal of Psychiatry article [Regier, et al., 2009], the use of dimensional assessments to reconceptualize psychopathology represents the most practical and evidence-based way of moving our field forward. Recent studies underscore the readiness of clinicians in both primary care and specialty mental health settings to adopt dimensional instruments on a routine basis [Duffy et al., 2008, Trivedi et al., 2006].

APA and DSM-V: Empty Promises

Psychiatric Times

By Robert L. Spitzer

July 02, 2009

[full text online]

I think it is likely true that the APA attorney declared that there was no conflict of interest in Dr. Kupfer’s actions detailed previously. While it’s hard to imagine what legal machinations the Attorney went through to come up with such an absurd conclusion, I’ve had my say about that multiple times. So for the moment, I want to talk about something else. Is a legal standard even appropriate to bring up in this case? We’re not talking about a person charged with a criminal offense going to trial or a civil suit alleging damages of one kind or another. And even in those situations, the opinion of a legal adviser isn’t the final word, it is only an opinion. Those verdicts comes from a Judge or a Jury.

In this case, the person under question is a high ranking official of the American Psychiatric Association tasked by the Board of Trustees to oversee a $25 M revision of the APA’s Diagnostic and Statistical Manual, a process over a decade in the making. The question is by what standard should such a person be judged. In the many debates about conflicts of interest over the life of the DSM-5 Revision process, the topic invariably revolved around the ties between DSM-5 Task Force members and the pharmaceutical industry – for example this point–counterpoint debate in the Psychiatric Times in 2009 involving Dr. Kupfer. The idea that a leader of the DSM-5 Task Force would be part of founding a company that produced screening instruments for things he was also supporting for inclusion in the manual never occurred to anyone. It was too outlandish to consider. But that’s what he did. And in an article about those tests in a peer reviewed journal, he omitted the required disclosure.

I presume that if we had the APA’s lawyer’s opinion, it would be something like: although the company was named, formed, incorporated in two states, professionally managed, and had a website, it had not yet officially launched its products, so technically that meant it wasn’t a conflict of interest. Something like that. That kind of technicality is well known to us from 20/20, or Mafia cases. This isn’t about such things. This is about medical ethics and integrity. And it’s not some Monica Lowensky dalliance – it’s in the direct line of duty. I can’t personally find a way to read this story as anything but profiteering. I gasped when I first heard it. Apparently the editor of JAMAPsychiatry did too, measured by the form of the published apology [Failure to Report Financial Disclosure Information]. I expect the members of the Board of Trustees at the APA gasped too [at least I hope so]. This wasn’t an ethical lapse. It was an active attempt to get away with something that went awry. No need to look at any rules to know that. Even if they had waited to incorporate their company until after the DSM-5 came out, or Kupfer had declared it along the way, it was still a misuse of his position for personal gain. There’s no piece of this caper that isn’t conduct unbecoming the chair of such an enterprise.

I guess I can take down the crossed fingers about the Open Letter to the APA concerning the Affaire d’Kupfer [see credibility…]. The Board of Trustees met three weeks ago and there hasn’t been a peep that I know about. After all the questions about conflicts of interest among members of the DSM-5 Task Force and Dr. Kupfer’s defensive responses, for him to turn out to have a significant hidden conflict of interest himself is bad enough. But for the APA’s Board of Trustees to simply ignore that it even happened takes things over the top. I expect there will come a day when they will regret that decision. I sure do already.

In legal terms, the facts of the incident are uncontested. Dr. Gibbons, a statistician at the University of Chicago adapted a method of psychometric testing to measure anxiety and depression using NIMH Grant funding. The Clinical testing was done under contract with Dr. Kupfer’s department of psychiatry in Pittsburgh. The focus of the psychometric was an aspect of diagnosis being championed by Dr. Kupfer as DSM-5 Task Force chairman – "dimensions." They published an article about the test, hiding the fact that they had formed a company to market the test commercially. When this was discovered and they were confronted, they admitted their culpability publicly. Four of the five authors were directly affiliated with the DSM-5 Task Force, with Dr. Kupfer as the chair. It is simply not possible that this was anything but active deceit. Those are the facts.

When all of this was revealed, the Speaker of the Assembly of the APA was asked to report on the incident to the APA Board of Trustees. She concluded that they shouldn’t have done it, but that it did no damage and the fact that Dr. Kupfer was involved did not offer commercial advantage to their company [that is, of course, an absurd conclusion]. There was no comment in the report that addressed the why of it – why he/they did it. And to return to my letter above, she did not address the ethical issues raised by this whole episode.

The traditional medical ethic is that physicians should not even have the appearance, much less an actual conflict of interest. In recent times, that standard has been downgraded to an injunction to declare conflicts of interest publicly. I for one feel that is an unwise loosening of standards. But to have a clear conflict of interest and keep it hidden is to ignore even this depreciated standard. And for the APA itself to not even see this as something to act on in the case of an official in an important position of authority within the APA is to essentially say that they have no ethical policy at all.

• Mistakes were made, Part 2
• the unforgotten unremembered…
• the twilight zone…
• Like Salem’s ‘witches,’ it’s time for NC to exonerate the Edenton Seven
• The Little Rascals Day Care Case
• Sex and Satanic Abuse: A Fad Revisited
• learning from mistakes…
• Psychiatric Times retracts essay on “satanic ritual abuse”
• perhaps bigger…
• of all people…
• Satanic Ritualistic Abuse – Revisited?
• the unforgetting…
• Psychiatric Times reinstates retracted essay on “satanic ritual abuse”

That last reference is to a newer post on Retraction Watch. Speak, Memory [AKA When Psychiatry Battled the Devil] has been un·retracted now for a week, and has gotten its good share of comments at Psychiatric Times. Most addressed, incredulously, that such a thing happened and/or the motives of those involved. As in the historical story of the Salem Witch Trials  or the oft-mentioned story of the Emperor’s New Clothes, in retrospect, such things do seem incredible, particularly when they’re of such a magnitude.

And as in this case, it’s easy to decry what happened through a lens of history. But that doesn’t fully do justice to what happened back there. And it doesn’t address the related phenomena all around us. In our film industry, this is hot stuff – vampires, horror films, aliens – the list goes on and on. In the westerns of my youth, there were good guys and bad guys [often identifiable by hat color]. And this metaphor that can be counted on in crime shows, murder mysteries, science fiction, and the current vampire/zombie productions that populate our cable channels. Embodiments of evil are all around us in our entertainment world, our political wranglings, our wars and their rhetoric.

I saw only one of these identified cases, in consultation. It was a long time ago, but she didn’t strike me as a person who was coming to see me for help with something – she seemed more to be looking for someone to go crazy with her. I passed on the offer. I doubt that such an n=1 example in any way characterizes the patients who were part of this story. Many seem to be like the passive and shy Sybil, caught up in her therapist’s story, desperate for an attachment. Truthfully, I can’t even speculate about the range of patient therapist dyads or groups involved because of limited to no experience, but the phenomena is certainly familiar. There are two kinds of injunctions in this regard. The first, "Listen to your patients. Don’t discount their stories." On the other side is something like, "Don’t take everything at face value. Everyone is looking for a champion." Freud’s answer was "neutrality." Stay in the middle, equidistant from the various possibilities without  joining any particular side. That’s a lot easier to say than do sometimes.

I once made up something I called my rule for living, "Never accept an invitation to go crazy." It was only partially tongue in cheek. I was dead serious too. The offers are everywhere, particularly in the mental health field, and this story of the SRA craze is an example of what happens if you don’t live by it, if we don’t live by it. I won’t go into why I was moved to make up such a rule, but it has to do with being willing to take on patients who struggle with more primitive mechanisms for living. They are often heroic indications for therapy, and success is never guaranteed – but very rewarding if achieved. But the rule stuck with me. My family even had it made into a coffee cup and bumper sticker because I say it so often.

Richard Noll has brought up a huge topic with this story. All of us have seen couples who have gone crazy together. We know about the Salem Witch Trials, Hitler’s Nazis, Religious Cults, Political Extremism, etc. We all watch some version of the good guy/bad guy media. If you’re a therapist and you can’t recall going crazy with some patient, you haven’t really put your feet in the water. It’s only through a retrospective look at our own stories that we can gain the skills to even approach our impossible profession with integrity. One thing I learned along the way. Whenever I felt the pull [whatever that means], I insisted on a consultation with someone [not in my inner circle]. And I did a lot of those consultations myself. It’s amazing how much a third pair of eyes can see when the fog of such things is in play between two people or within a group, something like a historical review [an outside opinion]. Secrecy or a closed shop is a real breeding ground for craziness becoming institutionalized.

I think I figured out why this particular topic is so interesting to me – to me specifically. I think of it is an explanation for what happened in psychiatry at large. Right now, there are plenty of people who would put all psychiatrists as a group into the category of satanic cults – motivated only by greed or worse.  And because of the subjective nature of the topic, we are particularly vulnerable to such. I wince when people write, "psychiatry thinks…" or when someone comments as if I think fill in the blank because I’m a psychiatrist [as we all think the same wrong things]. But that’s not what I was referring to. Mainstream psychiatry itself has been largely focused on the evil biology that afflicts humanity, and on a quest to root it out – even though it remains elusively out of view, to be uncovered in the future. There are a lot of very thoughtful biological psychiatrists and neuroscientists who are interested in and pursuing the biological underpinnings of some of the mental illnesses, but they have been marginalized by a larger group of people caught up in a craze – abetted by industrial forces and sexy new technology. Were I myself one of those biological psychiatrists, I would be furious at being trivialized by association with the people caught up in the monomaniacal crusade.

Drug regulator destroys Prozac research

The Sunday Times

by George Arbuthnott and Jonathan Leake

23 March 2014

The first time I ever prescribed Prozac was to the first HIV positive person I’d ever met.  He was a professor at a nearby university who had developed a lymphoma. As he was gay, his doctor suggested a brand new test [HIV], and it was positive. I’d never even heard of the test, and knew little about AIDS. At a later point, he wanted to try that new drug, Prozac. I read what there was to read, and we gave it a shot. His report was that it helped, but said he wasn’t sure it was an antidepressant. He called it an "anti-broodant." He didn’t "brood" about his plight so much. When the sexual side effects came, I went to the books again. "Rare" is what it said. He said, "’Well done’ is more like it!" and ultimately decided to stop, reporting that he felt bad coming off of it, but the bad feelings cleared after a time. So with this first patient, I learned about the anti-OCD effects of the drug, the sexual side effects, and about the withdrawal. He died from his primary illness before the modern treatments for AIDS came along.

MHRA destroys trial data after 15 years on file

PharmaTimes

by Kevin Grogan

March 24, 2014

The movement for more data transparency has been given a shot in the arm following a Sunday Times report which shows that the UK medicines regulator routinely destroys information on the licensing application files for drugs it has approved after 15 years. The newspaper’s piece documents the bid by Peter Gotzsche, co-founder of the Cochrane Collaboration, to get access to the data used to support marketing approval for Eli Lilly’s now off-patent antidepressant blockbuster Prozac [fluoxetine]. He approached the European Medicines Agency which referred him to the Medicines and Healthcare Products Regulatory Agency [MHRA] as the UK acted as the reference member state for Prozac approval.

However, the agency has shredded the vast majority of the clinical evidence it held on the treatment and the Prozac case is not an isolated one. Prof Gotzsche was told that “under MHRA record management policy, all application files and data for licences are held for 15 years". After this period, "files are destroyed unless there is a legal, regulatory, or business need to keep them, or unless they are considered to be of lasting historic interest". The Sunday Times article noted that “the MHRA said it had shredded the detailed information and held only some documents that summarised the findings". Lilly retains the data and the MHRA "can order it to be submitted".

Ben Goldacre, co-founder of AllTrials, said: “The MHRA needs to recognise that the world has changed, it is no longer acceptable for decisions about medicines to be based on secret meetings, about secret information that is then shredded". He added that "doctors, researchers and patients need access to all the evidence, to make fully informed decisions about which treatment is best, and help spot problems with treatments as quickly as possible". Dr Goldacre concluded by saying that "science progresses, and medicine improves, when we have many eyes on the data".

In response, an MHRA spokesperson told PharmaTimes that “we closely monitor the safety and efficacy of all medicines throughout the product lifecycle and we retain all key information relating to the agency’s assessment and decision-making processes". He added that "we use modern adverse drug reaction reporting systems and current research studies that better reflect clinical use and build on the original licensing data". He also stressed that the MHRA "has the legal power to require manufacturers of medicines to share safety, efficacy and clinical trial information from any time period so we can thoroughly investigate any issues".

Regarding the Prozac case specifically, the MHRA notes that it was "the first regulator to conduct a comprehensive safety review selective serotonin reuptake inhibitors [SSRIs] of the risks of suicidal behaviour and withdrawal reactions". It adds that "our overriding responsibility is to ensure that medicines work, and are acceptably safe. Our role is not to protect industry interests". The agency concludes by saying that "we are committed to greater transparency in our activities [and] we have already shown this by publishing the minutes of our advisory committees and Public Assessment Reports, detailing the processes and decisions made when licensing a drug and disclosing the evidence underpinning our decisions in areas of public concern."

What I was going to say above was that I want to know about all those early trials of the psychoactive drugs, and what they really showed. Every one of those studies is of "lasting historic interest." I’ve lived through a career without the traditional resources to learn from, including the academic department where I was a contributing member, a department chaired by Dr. Charles Nemeroff for twenty of the thirty years I’ve been a volunteer teacher – who sent me a letter every year thanking me for my service. During that time, almost everything I’ve learned about our medicines, I’ve learned from patients, particularly about the limited efficacy and the adverse effects. And it took a while to recognize that what I read in peer-reviewed journals was largely advertising pabulum.

It’s why I support the RIAT project [Restoring invisible and abandoned trials: a call for people to publish the findings]. That’s why I support AllTrials. I’d like to see critical analyses of all the drugs and trials that have come our way in the last twenty-seven years. Many of our critics point out that we [the physicians and psychiatrists] are the ones that wrote the prescriptions for every single pill taken, so I think we deserve to know definitively [whether we want to or not] what those clinical trials actually should have said – where those official guidelines and treatment algorithms actually came from. There is more than ample evidence that we were systematically deceived by the pharmaceutical industry and members of our own ranks who colluded with them and signed the articles that arose from those studies. That’s not to say that organized psychiatry and individual psychiatrists don’t also share in the blame.

… History will recognize Peter as the man who, among other achievements, pried open the question of access to RCT data, forcing the European Medicines’ Agency to open up their files. His motivation to do this came in part from a discovery of how appallingly bad the state of affairs in psychiatry IS. How almost all trials on which the field depends are ghostwritten, all data withheld and all dissent suppressed. Whatever it is this is not science and there has to be a good chance it’s killing and disabling more people prematurely than it helps.

What you hear from Peter is a howl of horror. The rest of us have got so inured to the situation we can no longer see how bad it is. The Allied troops arriving at concentration camps must have reacted the same way, where many inmates had gotten used to the situation…

I always feel an agita as March winds down. In the South, the trees and flowers begin to bloom in spite of periodic cold snaps. And for some of us, the antihistamines and daily checks on the pollen count come before the winter jackets move to the back of the closet. Then I remember why I feel flaky, and the memory actually helps, but always takes me by surprise. In 1968, it was a contentious time in Memphis where I lived – the garbage men went on strike. It was joined by the Civil Rights groups, and one Thursday in March, Dr. King came to town for a protest march which turned into a major riot – and we had martial law, curfews, gunfire was heard from my porch. Most of the violence before had come from white opposition to the Civil Rights Movement, but this one got started by the black militants who opposed MLK’s non-violent approach. However, once underway, everyone got in the act. It was the first march that King had lead that went so badly, and he vowed to return the following Thursday for another – it was to be a testimonial to non-violence.

I was an Intern and spent several days in the ER of the City Hospital treating casualties. Memphis was a wreck by then – garbage collecting at the curbs; people afraid to go out at night; racial tension at a fever pitch; soldiers on the streets; trees and flowers beginning to bloom. The next Thursday, we awoke to 14 inches of snow, and the march was postponed for a week. By the afternoon, the snow melted and the garbage spread down the streets as the runoff headed for the clogged drains. Over the next week, the tension continued to build. You all know what happened then – Martin Luther King was assassinated in the early evening on the eve of the march.

On the day it happened, I had been temporarily promoted and was acting as admitting resident because they had over-scheduled vacations. After dinner, my wife called and told me the news and took off for her brother’s house in a safer part of town. Then came a page to me that the ambulance was headed our way and I was to meet it. Anticipating the headlines, "Intern masquerading as Resident blows it in ER," I mobilized every doctor in the hospital to the ER. As it turned out, MLK was taken to another hospital on the way where a friend pronounced him dead. Then all hell broke loose. I’ve never been to war, but I call those next several days my Viet Nam. The ER was immediately filled with gun-shot people. Except for the wheels of the gurneys, it was silent as more wounded than I could imagine streamed in the doors. The cops were terrified. The patients were terrified. So were we. The floors were slippery with the blood that pored from the gunshot wounds. It went on for days.

I think about those days when people talk about the fog of war. My memories are seen through a vasoline covered lens and I rarely think of it except, like this morning, when I see an early Redbud, feel an unexplained emotional discomfort, and then I remember. I always feel like I’m being melodramatic when I talk about it, but it was real drama – at least as close as I ever get. When we finally went home three days later, we could hear  periodic gunshots, and tank convoys still rolled down our street. We were both committed to and involved in the Civil Rights Movement, but we were so caught up in the surround, and what was happening, that it would be a while before we could even think about the implications of that assassination. My friends who were in Viet Nam said the same thing coming home – they didn’t think about the why of that war while they were in it, only about managing the chaos of the days they were in.

These are not pleasant memories, but every year at about this time, I find myself telling this story to someone, or writing about it. I don’t think there’s a reason exactly. We all have memories of times like that – unpleasant stories, yet ones told repeatedly throughout life. I’ve come to believe that those experiences are a major part of the persons we’ve become, and even though the words can’t really convey the experience, the telling is vital to knowing who we are. Narrative, itself, is a psychotherapy. Thanks for listening…